【作者】 姚健；

【导师】 侯明晓；

【作者基本信息】 辽宁医学院 ， 外科学， 2012， 硕士

【摘要】 目的建立野百合碱（MCT）诱导大鼠肺动脉高压（PAH）动物模型，观测actemra对该模型肺动脉压、血清IL-6、survivin的影响，探讨其作用机制。方法1、分组方法：实验动物大鼠按体重随机分为三组： A.空白对照组（n=10）；B.实验对照组（n=10）；C. actemra干预组（n=10）。A组在第一天腹腔注射0.9%氯化钠注射液60mg/kg；B组在第一天腹腔注射MCT60mg/kg；C组在第一天腹腔注射MCT60mg/kg和actemra：5mg/kg。2、右心微导管测各组大鼠平均肺动脉压（mPAP）。3、HE染色观察各组大鼠肺组织标本的血管壁增厚情况。4、免疫组化观察IL-6和survivin在肺血管的表达情况。5、ELISA法定量测定血清IL-6和survivin的含量，综合评估actemra对MCT诱导PAH大鼠模型的影响。结果1、大鼠mPAP：Actemra干预组、空白对照组和实验对照组比较为（23.56±4.86）mmHg、（19.14±4.30）mmHg比（41.71±8.79）mmHg，p均<0.05。Actemra干预组和空白对照组比较无统计学意义，p>0.05。2、HE染色显示实验对照组肺动脉血管壁明显增厚，周围有炎性细胞浸润，肺泡间隔明显增厚。Actemra干预组肺动脉血管内膜轻度水肿，血管壁轻度增厚。3、免疫组化显示IL-6和survivin在实验对照组大鼠肺组织强表达，在Actemra干预组大鼠肺组织少量表达，而空白对照组大鼠肺组织不表达。4、ELISA定量测定IL-6含量：Actemra干预组和空白对照组明显低于实验对照组，组间比较为（1576.63±296.19）pg/ml、（1316.9798±71.20）pg/ml比（2069.49±295.60）pg/ml，p均<0.05。Survivin含量：Actemra干预组和空白对照组明显低于实验对照组，组间比较为（12.22±1.11）ng/ml、（2.40±3.62）ng/ml比（43.32±8.16）ng/ml，p均<0.05。结论1、Actemra可有效抑制MCT诱导PAH的发生。2、MCT诱导PAH产生可能与IL-6信号转导通路有关。更多还原

【Abstract】 ObjectiveThe purpose of this paper was through the establishment of monocrotaline(MCT)-induced pulmonary arterial hypertension (PAH) rat models, to observethe effects of actemra to model pulmonary artery pressure, serum IL-6andsurvivin, to investigate the mechanism.Method1. the grouping method: experimental rats were divided into three groupsrandomly: A. The blank control group (n=10); B. The experimental control group(n=10); C. the actemra intervention group (n=10). Group A: Intraperitonealinjection of0.9%saline on the first day; Group B: Intraperitoneal injection ofMCT (60mg/kg) on the first day; Group C: intraperitoneal injection of MCT(60mg/kg) and actemra (5mg/kg) on the first day.2. Using the right heart microcatheter measure mean pulmonary arterypressure (mPAP) of the rat in each group.3. Observation of rat lung tissue and vascular stenosis (or vascular wallthickening) by HE staining.4. Observation expression of IL-6and survivin in pulmonary vascular byimmunohistochemical staining.5. Quantitative determination level of serum IL-6and survivin by ELISA,and comprehensive assessment of actemra on MCT induced PAH rat model.Results1. MPAP of rats: mPAP both in actemra intervention group and blank control group lower then experimental control group[(23.56±4.86) mmHg(19.14±4.30) mmHg vs.(41.71±8.79) mmHg, p<0.05. mPAP in actemraintervention group and control group was not statistically significant, p>0.05.2. HE staining showed that the experimental control group had markedthickening of the pulmonary vascular wall, surrounded by inflammatory cellinfiltration, had marked thickening of alveolar septa. Pulmonary artery intimalmild edema and mild thicken vessel wall in actemra intervention group.3. Immunohistochemistry showed strong expression of IL-6and survivin inthe lung tissue in the experimental control, a small amount of expression in ratlungs in actemra intervention group, and did not express in blank control group.4. ELISA quantitative determination of IL-6levels: actemra interventiongroup and control group was significantly lower than the experimental controlgroup [(1576.63±296.19) pg/ml,(1316.9798±71.20) pg/ml vs.(2069.49±295.60)pg/ml p<0.05]. Survivin levels: actemra intervention group and blank controlgroup was lower than the experimental control group [(12.22±1.11) ng/ml,(2.40±3.62) ng/ml vs.(43.32±8.16) ng/ml, p <0.05].Conclusions1. Actemra could inhibit MCT induced PAH effectively.2. The generation of PAH induced by MCT may be associated with IL-6signal transduction pathway.更多还原